Role of the PU.1 transcription factor in controlling differentiation of friend erythroleukemia cells

Scott Schuetze, Ralph Paul, Brian C. Gliniak, David Kabat

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Both viral and cellular genes have been directly implicated in pathogenesis of Friend viral erythroleukemia. The virus-encoded gp55 glycoprotein binds to erythropoietin receptors to cause mitogenesis and differentiation of erythroblasts. However, if the provirus integrates adjacent to the gene for the PU.1 transcription factor, the cell loses its commitment to terminally differentiate and becomes immortal, as indicated by its transplantability and by its potential for indefinite growth in culture (C. Spiro, B. Gliniak, and D. Kabat, J. Virol. 63:4434-4437, 1989; R. Paul, S. Schuetze, S. L. Kozak, and D. Kabat, J. Virol. 65:464-467, 1991). To test the implications of these results, we produced polyclonal antiserum to bacterially synthesized PU.1, and we used it to analyze PU. 1 expression throughout leukemic progression and during chemically induced differentiation of Friend erythroleukemia (F-MEL) cell lines. This antiserum identified three electrophoretically distinct PU.1 components in extracts of F-MEL cells and demonstrated their nuclear localization. Although PU.1 proteins are abundant in F-MEL cells, they are absent or present in only trace amounts in normal erythroblasts or in differentiating erythroblasts from the preleukemic stage of Friend disease. Furthermore, chemicals (dimethyl sulfoxide or N,N-hexamethylenebisacetamide) that overcome the blocked differentiation of F-MEL cells induce rapid declines of PU.1 mRNA and PU.1 proteins. The elimination of PU.1 proteins coincides with recommitment to the program of erythroid differentiation and with loss of immortality. These results support the hypothesis that PU.1 interferes with the commitment of erythroblasts to differentiate and that chemicals that reduce PU.1 expression reinstate the erythropoietic program.

Original languageEnglish (US)
Pages (from-to)2967-2975
Number of pages9
JournalMolecular and Cellular Biology
Volume12
Issue number7
StatePublished - Jul 1992

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Erythroblasts
Leukemia, Erythroblastic, Acute
Transcription Factors
Immune Sera
Erythropoietin Receptors
Proviruses
Proteins
Viral Genes
Dimethyl Sulfoxide
Glycoproteins
Viruses
Cell Line
Messenger RNA
Growth
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Role of the PU.1 transcription factor in controlling differentiation of friend erythroleukemia cells. / Schuetze, Scott; Paul, Ralph; Gliniak, Brian C.; Kabat, David.

In: Molecular and Cellular Biology, Vol. 12, No. 7, 07.1992, p. 2967-2975.

Research output: Contribution to journalArticle

Schuetze, S, Paul, R, Gliniak, BC & Kabat, D 1992, 'Role of the PU.1 transcription factor in controlling differentiation of friend erythroleukemia cells', Molecular and Cellular Biology, vol. 12, no. 7, pp. 2967-2975.
Schuetze, Scott ; Paul, Ralph ; Gliniak, Brian C. ; Kabat, David. / Role of the PU.1 transcription factor in controlling differentiation of friend erythroleukemia cells. In: Molecular and Cellular Biology. 1992 ; Vol. 12, No. 7. pp. 2967-2975.
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